Schematic overview of the cellular and molecular mechanisms involved in the cancer progression, including the proposed cellular and molecular mechanisms in cancer cells trajectory. AT1: alveolar type 1 cells; AT2: alveolar type 2 cells; AAH: atypical adenomatous hyperplasia; AIS: adenocarcinoma in situ; MIA: minimally invasive adenocarcinoma; IA: invasive adenocarcinoma; EMT: epithelial-mesenchymal transition

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	Gene summary
	Malignant transformation analysis
	Malignant transformation related pathway analysis
	Cell-cell communication analysis
	Single-cell gene regulatory network inference analysis
	Somatic mutation of malignant transformation related genes
	Related drugs of malignant transformation related genes

Gene: FKBP4

Gene summary for FKBP4

Gene summary.

Gene information	Species	Human
	Gene symbol	FKBP4
	Gene ID	2288
	Gene name	FKBP prolyl isomerase 4
	Gene Alias	FKBP51
	Cytomap	12p13.33
	Gene Type	protein-coding
	GO ID	GO:0000041
	UniProtAcc	Q02790

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Malignant transformation analysis

Identification of the aberrant gene expression in precancerous and cancerous lesions by comparing the gene expression of stem-like cells in diseased tissues with normal stem cells

Malignant transformation involving gene list.

Entrez ID	Symbol	Replicates	Species	Organ	Tissue	Adj P-value	Log2FC	Malignancy
2288	FKBP4	CA_HPV_1	Human	Cervix	CC	4.33e-03	-6.15e-02	0.0264
2288	FKBP4	CA_HPV_3	Human	Cervix	CC	3.14e-03	2.27e-01	0.0414
2288	FKBP4	sample1	Human	Cervix	CC	1.08e-20	7.82e-01	0.0959
2288	FKBP4	T1	Human	Cervix	CC	3.96e-29	7.05e-01	0.0918
2288	FKBP4	HTA11_1938_2000001011	Human	Colorectum	AD	7.98e-03	2.07e-01	-0.0811
2288	FKBP4	HTA11_347_2000001011	Human	Colorectum	AD	2.61e-08	2.93e-01	-0.1954
2288	FKBP4	HTA11_3361_2000001011	Human	Colorectum	AD	1.26e-03	3.33e-01	-0.1207
2288	FKBP4	HTA11_866_2000001011	Human	Colorectum	AD	2.23e-04	1.77e-01	-0.1001
2288	FKBP4	HTA11_1391_2000001011	Human	Colorectum	AD	4.20e-07	3.19e-01	-0.059
2288	FKBP4	HTA11_866_3004761011	Human	Colorectum	AD	1.05e-02	1.87e-01	0.096
2288	FKBP4	HTA11_4255_2000001011	Human	Colorectum	SER	8.55e-04	3.42e-01	0.0446
2288	FKBP4	HTA11_7663_2000001011	Human	Colorectum	SER	1.78e-03	3.84e-01	0.0131
2288	FKBP4	HTA11_99999965062_69753	Human	Colorectum	MSI-H	1.91e-06	1.09e+00	0.3487
2288	FKBP4	HTA11_99999965104_69814	Human	Colorectum	MSS	2.05e-18	7.40e-01	0.281
2288	FKBP4	HTA11_99999971662_82457	Human	Colorectum	MSS	1.06e-08	3.38e-01	0.3859
2288	FKBP4	CRC-3-11773	Human	Colorectum	CRC	1.05e-04	3.27e-01	0.2564
2288	FKBP4	LZE2D	Human	Esophagus	HGIN	2.57e-02	-4.41e-02	0.0642
2288	FKBP4	LZE4T	Human	Esophagus	ESCC	7.57e-03	4.70e-01	0.0811
2288	FKBP4	LZE7T	Human	Esophagus	ESCC	2.31e-02	2.66e-01	0.0667
2288	FKBP4	LZE8T	Human	Esophagus	ESCC	1.24e-06	-8.21e-02	0.067

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Transcriptomic changes along malignancy continuum.

Tissue	Expression Dynamics	Abbreviation
Cervix		CC: Cervix cancer
		HSIL_HPV: HPV-infected high-grade squamous intraepithelial lesions
		N_HPV: HPV-infected normal cervix
Colorectum (GSE201348)		FAP: Familial adenomatous polyposis
		CRC: Colorectal cancer
Colorectum (HTA11)		AD: Adenomas
		SER: Sessile serrated lesions
		MSI-H: Microsatellite-high colorectal cancer
		MSS: Microsatellite stable colorectal cancer
Esophagus		ESCC: Esophageal squamous cell carcinoma
		HGIN: High-grade intraepithelial neoplasias
		LGIN: Low-grade intraepithelial neoplasias
GC		CAG: Chronic atrophic gastritis
		CAG with IM: Chronic atrophic gastritis with intestinal metaplasia
		CSG: Chronic superficial gastritis
		GC: Gastric cancer
		SIM: Severe intestinal metaplasia
		WIM: Wild intestinal metaplasia
Liver		HCC: Hepatocellular carcinoma
		NAFLD: Non-alcoholic fatty liver disease
Oral Cavity		EOLP: Erosive Oral lichen planus
		LP: leukoplakia
		NEOLP: Non-erosive oral lichen planus
		OSCC: Oral squamous cell carcinoma
Prostate		BPH: Benign Prostatic Hyperplasia
Skin		AK: Actinic keratosis
		cSCC: Cutaneous squamous cell carcinoma
		SCCIS:squamous cell carcinoma in situ
Thyroid		ATC: Anaplastic thyroid cancer
		HT: Hashimoto's thyroiditis
		PTC: Papillary thyroid cancer

∗log2FC in expression of this searched gene in stem-like cells from each diseased tissue sample relative to stem-like cells in normal samples in each tissue plotted against the malignancy continuum. Samples are colored based on if they are from different disease stage.

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Malignant transformation related pathway analysis

Find out the enriched GO biological processes and KEGG pathways involved in transition from healthy to precancer to cancer

Figure of enriched GO biological processes.

Tissue	Disease Stage	Enriched GO biological Processes
Thyroid	PTC
Thyroid	goiters
Thyroid	ATC

∗Top 15 enriched GO BP terms are showed in the bar plot of each disease state in each tissue. Each row represents a significant GO biological process which is colored according to the -log10(p.adjust).

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Enriched GO biological processes.

GO ID	Tissue	Disease Stage	Description	Gene Ratio	Bg Ratio	pvalue	p.adjust	Count
GO:190290310	Cervix	CC	regulation of supramolecular fiber organization	92/2311	383/18723	1.49e-10	2.48e-08	92
GO:004325410	Cervix	CC	regulation of protein-containing complex assembly	96/2311	428/18723	2.91e-09	3.05e-07	96
GO:005125810	Cervix	CC	protein polymerization	70/2311	297/18723	5.20e-08	3.11e-06	70
GO:003227110	Cervix	CC	regulation of protein polymerization	57/2311	233/18723	2.37e-07	1.03e-05	57
GO:00109757	Cervix	CC	regulation of neuron projection development	88/2311	445/18723	4.26e-06	1.09e-04	88
GO:19029048	Cervix	CC	negative regulation of supramolecular fiber organization	40/2311	167/18723	2.39e-05	4.17e-04	40
GO:00610779	Cervix	CC	chaperone-mediated protein folding	21/2311	67/18723	3.40e-05	5.55e-04	21
GO:00313339	Cervix	CC	negative regulation of protein-containing complex assembly	35/2311	141/18723	3.41e-05	5.55e-04	35
GO:00106399	Cervix	CC	negative regulation of organelle organization	68/2311	348/18723	7.40e-05	1.03e-03	68
GO:00514948	Cervix	CC	negative regulation of cytoskeleton organization	37/2311	163/18723	1.57e-04	1.88e-03	37
GO:00064579	Cervix	CC	protein folding	44/2311	212/18723	3.43e-04	3.59e-03	44
GO:00313456	Cervix	CC	negative regulation of cell projection organization	39/2311	186/18723	5.86e-04	5.57e-03	39
GO:00705074	Cervix	CC	regulation of microtubule cytoskeleton organization	32/2311	148/18723	1.02e-03	8.51e-03	32
GO:00322728	Cervix	CC	negative regulation of protein polymerization	20/2311	80/18723	1.40e-03	1.10e-02	20
GO:00311134	Cervix	CC	regulation of microtubule polymerization	15/2311	55/18723	2.14e-03	1.54e-02	15
GO:00109775	Cervix	CC	negative regulation of neuron projection development	28/2311	137/18723	4.74e-03	2.83e-02	28
GO:00467853	Cervix	CC	microtubule polymerization	19/2311	83/18723	5.25e-03	3.08e-02	19
GO:0031111	Cervix	CC	negative regulation of microtubule polymerization or depolymerization	11/2311	40/18723	7.54e-03	4.02e-02	11
GO:00311101	Cervix	CC	regulation of microtubule polymerization or depolymerization	19/2311	88/18723	1.01e-02	4.91e-02	19
GO:1902903	Colorectum	AD	regulation of supramolecular fiber organization	139/3918	383/18723	2.01e-12	3.19e-10	139

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Enriched KEGG pathways.

Pathway ID	Tissue	Disease Stage	Description	Gene Ratio	Bg Ratio	pvalue	p.adjust	qvalue	Count
hsa0491520	Cervix	CC	Estrogen signaling pathway	44/1267	138/8465	3.55e-07	3.97e-06	2.35e-06	44
hsa04915110	Cervix	CC	Estrogen signaling pathway	44/1267	138/8465	3.55e-07	3.97e-06	2.35e-06	44
hsa04915	Colorectum	SER	Estrogen signaling pathway	38/1580	138/8465	6.51e-03	3.68e-02	2.67e-02	38
hsa049151	Colorectum	SER	Estrogen signaling pathway	38/1580	138/8465	6.51e-03	3.68e-02	2.67e-02	38
hsa049152	Colorectum	MSS	Estrogen signaling pathway	48/1875	138/8465	4.23e-04	3.08e-03	1.89e-03	48
hsa049153	Colorectum	MSS	Estrogen signaling pathway	48/1875	138/8465	4.23e-04	3.08e-03	1.89e-03	48
hsa049154	Colorectum	CRC	Estrogen signaling pathway	29/1091	138/8465	4.83e-03	2.66e-02	1.80e-02	29
hsa049155	Colorectum	CRC	Estrogen signaling pathway	29/1091	138/8465	4.83e-03	2.66e-02	1.80e-02	29
hsa0491529	Oral cavity	EOLP	Estrogen signaling pathway	38/1218	138/8465	3.78e-05	1.82e-04	1.07e-04	38
hsa04915113	Oral cavity	EOLP	Estrogen signaling pathway	38/1218	138/8465	3.78e-05	1.82e-04	1.07e-04	38
hsa0491527	Prostate	BPH	Estrogen signaling pathway	48/1718	138/8465	4.60e-05	3.16e-04	1.96e-04	48
hsa04915112	Prostate	BPH	Estrogen signaling pathway	48/1718	138/8465	4.60e-05	3.16e-04	1.96e-04	48
hsa0491528	Prostate	Tumor	Estrogen signaling pathway	48/1791	138/8465	1.36e-04	8.33e-04	5.17e-04	48
hsa0491536	Prostate	Tumor	Estrogen signaling pathway	48/1791	138/8465	1.36e-04	8.33e-04	5.17e-04	48
hsa0491512	Stomach	GC	Estrogen signaling pathway	23/708	138/8465	1.02e-03	7.44e-03	5.23e-03	23
hsa0491513	Stomach	GC	Estrogen signaling pathway	23/708	138/8465	1.02e-03	7.44e-03	5.23e-03	23
hsa0491521	Stomach	CAG with IM	Estrogen signaling pathway	21/640	138/8465	1.53e-03	1.01e-02	7.10e-03	21
hsa0491531	Stomach	CAG with IM	Estrogen signaling pathway	21/640	138/8465	1.53e-03	1.01e-02	7.10e-03	21
hsa0491541	Stomach	CSG	Estrogen signaling pathway	20/633	138/8465	3.10e-03	1.88e-02	1.35e-02	20
hsa0491551	Stomach	CSG	Estrogen signaling pathway	20/633	138/8465	3.10e-03	1.88e-02	1.35e-02	20

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Cell-cell communication analysis

Identification of potential cell-cell interactions between two cell types and their ligand-receptor pairs for different disease states

Ligand

Receptor

LRpair

Pathway

Tissue

Disease Stage

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Single-cell gene regulatory network inference analysis

Find out the significant the regulons (TFs) and the target genes of each regulon across cell types for different disease states

Cell Type

Tissue

Disease Stage

Target Gene

RSS

Regulon Activity

∗The dot plots of a searched regulon are shown for all cell subpopulations in each disease state of each tissue based on the regulon specific score inferred using pySCENIC and by calculating the average expression.

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Somatic mutation of malignant transformation related genes

Annotation of somatic variants for genes involved in malignant transformation

Hugo Symbol

Variant Class

Variant Classification

dbSNP RS

HGVSc

HGVSp

HGVSp Short

SWISSPROT

BIOTYPE

SIFT

PolyPhen

Tumor Sample Barcode

Tissue

Histology

Sex

Age

Stage

Therapy Types

Drugs

Outcome

FKBP4

SNV

Missense_Mutation

c.557G>A

p.Arg186Gln

p.R186Q

Q02790

protein_coding

deleterious(0)

probably_damaging(0.985)

TCGA-A2-A0CL-01

Breast

breast invasive carcinoma

Female

<65

III/IV

Chemotherapy

cytoxan

FKBP4

SNV

Missense_Mutation

novel

c.1223N>G

p.Lys408Arg

p.K408R

Q02790

protein_coding

tolerated(0.26)

benign(0.159)

TCGA-A7-A4SD-01

Breast

breast invasive carcinoma

Female

<65

I/II

Chemotherapy

taxotere

FKBP4

SNV

Missense_Mutation

novel

c.766N>C

p.Lys256Gln

p.K256Q

Q02790

protein_coding

deleterious(0)

possibly_damaging(0.881)

TCGA-BH-A0HU-01

Breast

breast invasive carcinoma

Female

<65

I/II

Chemotherapy

docetaxel

FKBP4

SNV

Missense_Mutation

c.1108G>A

p.Glu370Lys

p.E370K

Q02790

protein_coding

deleterious(0.04)

benign(0.058)

TCGA-EA-A1QS-01

Cervix

cervical & endocervical cancer

Female

<65

I/II

Unknown

FKBP4

SNV

Missense_Mutation

c.823G>C

p.Glu275Gln

p.E275Q

Q02790

protein_coding

tolerated(0.08)

benign(0.428)

TCGA-EK-A2H0-01

Cervix

cervical & endocervical cancer

Female

<65

I/II

Chemotherapy

cisplatin

FKBP4

SNV

Missense_Mutation

c.26C>T

p.Thr9Ile

p.T9I

Q02790

protein_coding

tolerated(0.18)

benign(0.017)

TCGA-Q1-A73P-01

Cervix

cervical & endocervical cancer

Female

<65

I/II

Unknown

FKBP4

SNV

Missense_Mutation

c.823G>C

p.Glu275Gln

p.E275Q

Q02790

protein_coding

tolerated(0.08)

benign(0.428)

TCGA-ZJ-A8QQ-01

Cervix

cervical & endocervical cancer

Female

<65

I/II

Chemotherapy

cisplatin

FKBP4

SNV

Missense_Mutation

novel

c.976G>T

p.Ala326Ser

p.A326S

Q02790

protein_coding

deleterious(0.04)

possibly_damaging(0.59)

TCGA-ZJ-AAX8-01

Cervix

cervical & endocervical cancer

Female

<65

III/IV

Unknown

FKBP4

insertion

Frame_Shift_Ins

novel

c.372dupC

p.Asn125GlnfsTer7

p.N125Qfs*7

Q02790

protein_coding

TCGA-EA-A3HU-01

Cervix

cervical & endocervical cancer

Female

<65

I/II

Unknown

FKBP4

SNV

Missense_Mutation

rs766636474

c.1343N>T

p.Thr448Met

p.T448M

Q02790

protein_coding

tolerated_low_confidence(0.16)

benign(0)

TCGA-A6-2686-01

Colorectum

colon adenocarcinoma

Female

>=65

I/II

Unknown

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Related drugs of malignant transformation related genes

Identification of chemicals and drugs interact with genes involved in malignant transfromation

(DGIdb 4.0)

Entrez ID	Symbol	Category	Interaction Types	Drug Claim Name	Drug Name	PMIDs
2288	FKBP4	DRUGGABLE GENOME		IMMUNOSUPPRESSIVE		1716886
2288	FKBP4	DRUGGABLE GENOME		RAPAMYCIN	SIROLIMUS	1700475

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